title: Hepatocyte growth factor acutely perturbs actin filament anchorage at the epithelial zonula adherens.
abstract: Cadherin adhesion molecules function in close cooperation with the actin cytoskeleton. At the zonula adherens (ZA) of polarized epithelial cells, E-cadherin adhesion induces the cortical recruitment of many key cytoskeletal regulators, which act in a dynamic integrated system to regulate junctional integrity and cell-cell interactions. This capacity for the cytoskeleton to support the ZA carries the implication that regulators of the junctional cytoskeleton might also be targeted to perturb junctional integrity. In this report, we now provide evidence for this hypothesis. We show that hepatocyte growth factor (HGF), which is well-known to disrupt cell-cell interactions, acutely perturbs ZA integrity much more rapidly than generally appreciated. This is accompanied by significant loss of junctional F-actin, a process that reflects loss of filament anchorage at the junctions. We demonstrate that this involves uncoupling of the unconventional motor myosin VI from junctional E-cadherin, a novel effect of HGF that is mediated by intracellular calcium. We conclude that regulators of the junctional cytoskeleton are likely to be major targets for cadherin junctions to be acutely modulated in development and perturbed in disease.
authors.affiliation: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mangold
authors.forename: Selwin K
authors.initials: SK
authors.lastname: Wu
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Norwood
authors.forename: Brett M
authors.initials: BM
authors.lastname: Collins
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Hamilton
authors.forename: Peter
authors.initials: P
authors.lastname: Thorn
authors.forename: Alpha S
authors.initials: AS
authors.lastname: Yap
mesh_terms: D000199:Actins / Q000378:metabolism*; D022005:Adherens Junctions / Q000502:physiology*; D015153:Blotting, Western; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000378:metabolism*; D004848:Epithelium / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction
chemical_list: D000199:Actins; D015820:Cadherins; C089785:myosin VI; D017228:Hepatocyte Growth Factor; D018995:Myosin Heavy Chains; D002118:Calcium